Acute pulmonary embolism (PE) remains a diagnostic and therapeutic challenge, with an estimated 60,000-100,000 deaths each year in the United States.¹ Although the management of high-risk PE frequently involves systemic thrombolytics, the optimal approach for individuals at high risk who have contraindications to thrombolytics and those with intermediate-risk PE remains uncertain. In intermediate-risk PE, fibrinolytic therapy had lower rates of death or hemodynamic collapse than did standard anticoagulation; however, it was at a cost of higher bleeding rates.² Catheter-directed thrombolytics (CDT) resulted in a reduction in all-cause mortality and an improvement in the right ventricular/left ventricular ratio compared with systemic anticoagulation.³ Large-bore mechanical thrombectomy (LBMT) registry data have shown a low all-cause mortality.⁴ However, there has been a lack of randomized controlled trials in this area.

The PEERLESS (Large-Bore Mechanical Thrombectomy vs. Catheter-Directed Thrombolysis for Treatment of Intermediate-Risk Pulmonary Embolism) trial was a multicenter trial in which 550 patients were randomized to LBMT or CDT.⁵ The primary endpoint was a hierarchical win ratio composite of all-cause death, intracranial hemorrhage, major bleeding, clinical deterioration and/or escalation to bailout, postprocedural intensive care unit (ICU) admission, and length of stay. LBMT was associated with lower rates of the primary outcome compared with CDT (win ratio, 5.01 [95% confidence interval, 3.68-6.97]; p < 0.001), primarily due to lower rates of clinical deterioration (1.8% vs. 5.4%; p = 0.04), less postprocedural ICU utilization (41.6% vs. 98.6%; p < 0.001), and lower 30-day readmissions (3.2% vs. 7.9%; p = 0.03). There were no differences in mortality, intracranial hemorrhage, or major bleeding.

The PEERLESS trial is the first to compare two catheter-based interventions for patients with acute intermediate-risk PE, with the findings supporting the use of LBMT over CDT when evaluated using a win ratio of hierarchical endpoints. Although no significant difference in mortality was observed between the two treatment groups, LBMT was noted to have lower hospital resource utilization, reducing both ICU utilization and readmission rates. The therapeutic efficacy of catheter-based interventions relative to the standard of care remains unclear, with future trials aiming to address this question: the HI-PEITHO (Ultrasound-facilitated, Catheter-directed, Thrombolysis in Intermediate-high Risk Pulmonary Embolism), PE-TRACT (Pulmonary Embolism - Thrombus Removal With Catheter-Directed Therapy), and PEERLESS II (RCT of FlowTriever vs. Anticoagulation Alone in Pulmonary Embolism).

References

1. Freund Y, Cohen-Aubart F, Bloom B. Acute pulmonary embolism: a review. JAMA 2022;328:1336-45.
2. Meyer G, Vicaut E, Danays T, et al.; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014;370:1402-11.
3. Sadeghipour P, Jenab Y, Moosavi J, et al. Catheter-directed thrombolysis vs anticoagulation in patients with acute intermediate-high-risk pulmonary embolism: the CANARY randomized clinical trial. JAMA Cardiol 2022;7:1189-97.
4. Toma C, Jaber WA, Weinberg MD, et al. Acute outcomes for the full US cohort of the FLASH mechanical thrombectomy registry in pulmonary embolism. EuroIntervention 2023;18:1201-12.
5. Jaber WA, Gonsalves CF, Stortecky S, et al.; PEERLESS Committees and Investigators. Large-bore mechanical thrombectomy versus catheter-directed thrombolysis in the management of intermediate-risk pulmonary embolism: primary results of the PEERLESS randomized controlled trial. Circulation 2024;Oct 29:[ePub ahead of print].